Chronic calorie restriction increases susceptibility of laboratory mice (Mus musculus) to a primary intestinal parasite infection

Abstract

SummaryLong-term calorie restriction (CR) has numerous benefits; however, effects of CR on susceptibility to intact pathogens are not well understood. Because CR enhances immune function of laboratory mice ( Mus musculus ), it was hypothesized that mice subjected to CR would be less susceptible to experimental infections of the intestinal parasite Heligmosomoides bakeri . Furthermore, because H. bakeri must combat a greater host immune response by CR mice compared to fully fed mice, it also was also hypothesized that (i) worms living in CR hosts would have lower reproduction than worms from ad libitum -fed mice, and (ii) CR mice would have a more female-biased sex ratio as male worms may be more vulnerable to host immune response than female worms. Mice were subjected to CR for 6.7 months and were then infected with H. bakeri for one additional month. As expected, CR mice had equal or enhanced immune response (eosinophils and immunoglobin G1 production) to H. bakeri infection compared to ad libitum -fed mice, and CR mice harbored a more femalebiased sex ratio than ad libitum -fed mice. Contrary to predictions, CR mice had more worms than ad libitum -fed mice and the worms from CR mice produced more eggs than worms from ad libitum -fed mice. These data indicate that, despite the evidence that long-term CR enhances traditional measures of immune function, CR may actually increase susceptibility to intact parasite infection. Furthermore, changes in worm reproduction and differential survival of male vs. female worms may influence hostparasite transmission dynamics during long-term host CR.

Genes regulated by caloric restriction have unique roles within transcriptional networks

“…All things considered, the most important investigations are those focused on survival and disease susceptibility of CR-treated animals following exposure to pathogens. In this regard, CR decreased survival of aged mice following primary exposure to influenza (Gardner, 2005), and a recent study showed that CR-treated mice were more susceptible to infection by an intestinal parasite (Kristan, 2007). A possible explanation of these results is that the low body weight of CR-treated mice fails to provide energetic resources to meet the metabolic costs of infection and immune response (Ritz and Gardner, 2006).…”

Integrating nutrition and immunology: A new frontier

“…As in the previous example, starvation and energy restriction have typically been used to measure the effects of nutrition on immunity (Kristan, 2007;Murray and Murray, 1979). In insects, experimental studies have demonstrated that food deprivation of the host leads to reduced immune responsiveness (e.g.…”

“…First, immune function is affected by host nutrition, which may greatly affect the outcome of infection (Lazzaro and Little, 2009;Schmid-Hempel, 2011). Host nutrition influences both constitutive and inducible immune function, with consequences for morbidity and mortality (Cunningham-Rundles et al, 2005;Klasing, 2007) (Adams and Hewison, 2008;Amar et al, 2007;Calder, 2006;Cohen et al, 2008;Kelley and Bendich, 1996;Klasing, 2007;Kolb, 1997;Kristan, 2007;Samartin and Chandra, 2000;Sorci and Faivre, 2009). Second, nutrition-based interactions are one of the major sources of microbial benefits to animals (Bäckhed et al, 2005;Douglas, 2010;Hooper et al, 2002;Kau et al, 2011;Topping and Clifton, 2001).…”

Calorie restriction and susceptibility to intact pathogens

“…Work in my lab showed that after 6.7 months of CR, mice were more susceptible than AL mice to a primary exposure of Heligmosomoides bakeri, a nematode worm that resides in the mouse small intestine (Kristan 2007). The greater number of adult worms found in CR compared to AL mice was likely due to enhanced adult worm survival, since larval establishment was similar in another experiment comparing AL and CR mice (D.M.…”